Extracellular pH is a biomarker enabling detection of breast cancer and liver cancer using CEST MRI
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Miaomiao Chen1,*, Chaoying Chen2,*, Zhiwei Shen1, Xiaolei Zhang1, Yanzi Chen1, Fengfeng Lin1, Xilun Ma1, Caiyu Zhuang1, Yifei Mao1, Haochuan Gan1, Peidong Chen1, Xiaodan Zong1 and Renhua Wu1,3
1Department of Medical Imaging, The Second Affiliated Hospital, Medical College of Shantou University, Shantou 515041, China
2Department of Clinical Laboratory, The First Affiliated Hospital of Hunan Traditional Chinese Medical College, Zhuzhou 412000, China
3Provincial Key Laboratory of Medical Molecular Imaging, Shantou 515041, China
*These authors have contributed equally to this work
Renhua Wu, email: [email protected]
Keywords: liver cancer, pH imaging, breast cancer, ioversol, CEST MRI
Received: January 24, 2017 Accepted: April 03, 2017 Published: April 25, 2017
Extracellular pH (pHe) decrease is associated with tumor growth, invasion, metastasis, and chemoresistance, which can be detected by chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI). Here, we demonstrated that ioversol CEST MRI can be exploited to achieve pHe mapping of the liver cancer microenvironment. In in vitro studies, we firstly explored whether ioversol signal is pH-dependent, and calculated the function equation between the CEST effects of ioversol and pH values, in the range of 6.0 to 7.8, by a ratiometric method. Then we verified the feasibility of this technique and the equation in vivo by applying pHe imaging in an MMTV-Erbb2 transgenic mouse breast cancer model, which is often used in CEST pHe studies. Furthermore, in vivo ioversol CEST MRI, we were able to map relative pHe and differentiate between tumor and normal tissue in a McA-RH7777 rat hepatoma model. This suggests pHe may be a useful biomarker for human liver cancer.
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